Gold–silica quantum rattles for multimodal imaging and therapy

Abstract

Gold quantum dots exhibit distinctive optical and magnetic behaviors compared with larger gold nanoparticles. However, their unfavorable interaction with living systems and lack of stability in aqueous solvents has so far prevented their adoption in biology and medicine. Here, a simple synthetic pathway integrates gold quantum dots within a mesoporous silica shell, alongside larger gold nanoparticles within the shell's central cavity. This "quantum rattle" structure is stable in aqueous solutions, does not elicit cell toxicity, preserves the attractive near-infrared photonics and paramagnetism of gold quantum dots, and enhances the drug-carrier performance of the silica shell. In vivo, the quantum rattles reduced tumor burden in a single course of photothermal therapy while coupling three complementary imaging modalities: near-infrared fluorescence, photoacoustic, and magnetic resonance imaging. The incorporation of gold within the quantum rattles significantly enhanced the drug-carrier performance of the silica shell. This innovative material design based on the mutually beneficial interaction of gold and silica introduces the use of gold quantum dots for imaging and therapeutic applications.nanomedicine | hybrid nanoparticle | cancer nanotechnology | gold quantum dots | mesoporous silica A lthough gold's potential in nanotechnology has been recognized for many decades (1, 2), new insights into the unique properties of gold nanoparticles (NPs) of less than 2 nm have just recently started to emerge (3, 4). Such extremely small gold NPs could be transformative for a broad set of applications ranging from energy production and storage to catalysis and health care (3). As the size of gold NPs decreases below 2 nm, the quantization of their conduction band leads to molecule-like properties (3). These quantum-sized gold NPs (or gold quantum dots, AuQDs) absorb light in the near-infrared (NIR) biological window (650-900 nm) (2) and convert it into photons and heat (5). Furthermore, whereas bulk gold is diamagnetic, some AuQDs exhibit magnetic properties (4, 6). However, the clear therapeutic and imaging potential of AuQDs in vivo has been undermined by their unfavorable biointeractions and lack of stability in aqueous solvents (5, 7). In biological environments AuQDs tend to aggregate rapidly, reverting to larger gold nanoparticles (AuNPs) (8) and/or bind to protein, which negatively affects their cytotoxicity (7). To retain their advantages, AuQDs require a protective, stabilizing framework that allows proficient biological interactions.Recently, new emphasis has been placed on hybrid NP systems, where multiple nanomaterials are assembled to create multimodal systems that exhibit the combined qualities of the component modules (9-11). These constructs promise to integrate various functionalities by incorporating different nanomaterials into a single, efficient, multimodal system (12, 13). However, these systems usually accumulate the specific functionalities of their component modules through multiple steps in their ...

Optical Properties of Hybrid Organic‐Inorganic Materials and their Applications

“…It was recently demonstrated that incorporation of such AuQDs into hollow mesoporous silica nanoparticles (Quantum rattles QRs) is an alternative to stabilize the metal while preserving its specific optical and magnetic properties. [468] The QRs were successfully used for multimodal imaging (Fluorescence, photoacoustic), drug delivery and photothermal therapy of tumors (Figure 41). Hybrid materials using specific responses of stabilized small metal NPs, which have not been fully explored yet, represent certainly a wide range of possible future innovations routes in the fields of nanomedicine or catalysis.…”

Advanced optoacoustic methods for multiscale imaging of in vivo dynamics

“…In particular, nanostructures providing high absorption in the NIR range include copper sulphide NPs [197–199], palladium nanosheets [200] or upconversion NPs [201–203]. Quantum dots are semiconductor nanocrystals with excellent fluorescence brightness that can also be used as optoacoustic contrast agents [204, 205], while carbon dots further represent a less toxic alternative with similar absorption characteristics [206]. Many NPs originally designed for non-optical imaging modalities may still have prominent light absorption properties, suggesting their use as multimodal contrast agents.…”

Fluorescent Gold Nanoclusters: Promising Fluorescent Probes for Sensors and Bioimaging

“…The obtained AuNCs could be used for triple-modal FI/MRI/X-ray computed tomography (CT) imaging. Hembury and coworkers reported a simple synthetic route based on the mutually beneficial interaction of Au and SiO 2 [143]. This SiO 2 /AuNCs possessed stable NIR fluorescence and paramagnetism.…”